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A series or substituted xanthones was synthesized in order to prove the hypothesis that electron-withdrawing substituents enhance the antimycobacterial activity of these compounds, which is described by means of a QSAR equation with 13 C NMR chemical shifts as independent parameters. The key step of the synthesis is the formation of substituted 2-phenoxybenzoic acids by Ullmann reaction followed by intramolecular Friedel-Crafts acylation, leading to methyl-, carboxy-, nitro-, cyano-, and aminoxanthones as a test set for QSAR investigations. Spectroscopic data ( 1 H and 13 C chemical shifts, IR, UV) of these xanthones are presented and analyzed. Specific shift increments for xanthones depending on the substituent position and on the position of the respective proton/carbon atom as well as additivity rules were developed.

A series of substituted xanthones was tested for their activity against four mycobacterial strains (Mycobacterium tuberculosis, M. avium, M. lufu, M. smegmatis) by determination of the minimum inhibitory concentrations (MIC values). For the most active compounds, supplementary characterisation was performed by bacterial growth kinetics, which allows a more precise interpretation of their antimycobacterial effects. From the test set, 1-methyl-2,4,7-trinitroxanthone (8a) showed the highest antimycobacterial activity with a MIC value of 3 micrograms/mL against M. tuberculosis, which is comparable to the effect of well known drugs used in the treatment of tuberculosis. For all other compounds, the MIC values could not be determined, due to the comparatively low activity and to the poor solubility of the compounds, respectively. The semiquantitative evaluation of activity against the different strains of mycobacteria resulted in a classification into three activity classes, which will be used as dependent parameter in QSAR investigations, to be published in Part 3 of this series.

A series of substituted xanthones was tested for their activity against four mycobacterial strains (Mycobacterium tuberculosis, M. avium, M. lufu, M. smegmatis) by determination of the minimum inhibitory concentrations (MIC values). For the most active compounds, supplementary characterisation was performed by bacterial growth kinetics, which allows a more precise interpretation of their antimycobacterial effects. From the test set, 1-methyl-2,4,7-trinitroxanthone (8a) showed the highest antimycobacterial activity with a MIC value of 3 micrograms/mL against M. tuberculosis, which is comparable to the effect of well known drugs used in the treatment of tuberculosis. For all other compounds, the MIC values could not be determined, due to the comparatively low activity and to the poor solubility of the compounds, respectively. The semiquantitative evaluation of activity against the different strains of mycobacteria resulted in a classification into three activity classes, which will be used as dependent parameter in QSAR investigations, to be published in Part 3 of this series.